免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

Study Description
Brief Summary:
To exam in the effect of a combination of low dose Metformin and Spironolactone on functional brain MRI, menstrual regulation and metabolism in adolescents with PCOS.

Condition or disease Intervention/treatment Phase
PCOS Drug: Metformin and Spironolactone Phase 2 Phase 3

Detailed Description:

Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in adolescent females and also one of the most complex. Patients experience an exaggerated ovarian/adrenal androgen production in response to physiologic and supra-physiologic elevations in insulin. The hormonal dysregulation is not only associated with acne, hirsutism, and menstrual irregularity, but also with perpetuated insulin resistance, central adiposity, and clinical depression.

In the proposed study, we aim to treat a hormonally and metabolically well-defined group of adolescent girls with PCOS with a combination of two pharmacological agents: metformin (insulin sensitizer) and spironolactone (anti-androgen) for 6 months. Although hyperandrogenism is a fundamental component of PCOS and responsible for the perpetuation of insulin resistance, adiposity and anovulation, there are few pediatric studies that have examined the benefits of treating both insulin resistance and hyperandrogenism simultaneously. Preliminary studies in adults, however, suggest synergistic effect of both spironolactone and metformin (spiro-met) with near normalization of the metabolic and ovulatory dysfunction. Therefore, we hypothesize that spiro-met will improve adolescent metabolism, body composition, ovarian morphology/function. We anticipate that our study will generate key pilot data for further randomized, double blind placebo controlled trials using both agents.

We also plan to examine functional brain MRI before and after the spiro-met intervention. This will allow us to inspect the effects of the hyperinsulinemic/androgenic hormonal milieu in PCOS on structural and functional brain MRI. We hypothesis, that the hormonal environment in PCOS affects centers of appetite and mood.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents
Actual Study Start Date : July 2, 2016
Actual Primary Completion Date : July 9, 2018
Actual Study Completion Date : June 5, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: Overall Study
Treatment with Metformin and Spironolactone
 Drug: Metformin and Spironolactone
Oral Metformin tablet (500 mg/tablet) twice daily for 6 months. Oral Spironolactone tablet (50 mg/tablet) once daily for 6 months.
Outcome Measures
Primary Outcome Measures :
  1. Oral Glucose Tolerance Test [ Time Frame: Change Measures: Baseline & 6 Months ]
    Measurement of glucose and insulin at baseline and 2 hours after 75g of glucola.

  2. Total Testosterone [ Time Frame: Change Measures: Baseline & 6 Months ]
    Total Testosterone measured in ng/dL

  3. Free Testosterone [ Time Frame: Change Measures: Baseline & 6 Months ]
    Free Testosterone measured in ng/dL

  4. Dehydroepiandrosterone Sulfate (DHEAS) [ Time Frame: Change Measures: Baseline & 6 Months ]
    DHEAS measured in mcg/dL

  5. Body Mass Index (BMI) [ Time Frame: Change Measures: Baseline & 6 Months ]
    Body Mass Index measured in kg/m2


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   13 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Generally healthy
  • Meeting Androgen Excess Society (AES) diagnostic criteria of PCOS: Menstrual Dysfunction or PCO ovaries on ultrasound AND clinical or biochemical hyperandrogenism
  • Normal liver and kidney function
  • No chronic illnesses except for stable, treated hypothyroidism

Exclusion Criteria:

  • Use of metformin and/or spironolactone within the last 6 months
  • Currently on either oral hormonal contraception or other forms of hormonal contraception such as Depo-Provera, NuvaRing
  • Current or past pregnancy
  • Currently sexually active
  • Psychiatric disorder based on self/parental report
  • Type 2 diabetes (blood glucose > 200mg/dl on OGTT)
  • Anemia (Hct < 35)
  • Impaired kidney function (Baseline creatinine > 1.0 mg)
  • Abnormal liver transaminases > 2 x the upper limit of normal range
  • Potassium elevated outside the reference range (in non-hemolyzed blood sample)
Contacts and Locations

Locations
Layout table for location information
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
Investigators
Layout table for investigator information
Principal Investigator: Tania Burgert, MD Children's Mercy Hospital Kansas City
Tracking Information
First Submitted Date  ICMJE June 7, 2019
First Posted Date  ICMJE June 11, 2019
Results First Submitted Date  ICMJE December 18, 2020
Results First Posted Date  ICMJE February 23, 2021
Last Update Posted Date February 23, 2021
Actual Study Start Date  ICMJE July 2, 2016
Actual Primary Completion Date July 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2021)
  • Oral Glucose Tolerance Test [ Time Frame: Change Measures: Baseline & 6 Months ]
    Measurement of glucose and insulin at baseline and 2 hours after 75g of glucola.
  • Total Testosterone [ Time Frame: Change Measures: Baseline & 6 Months ]
    Total Testosterone measured in ng/dL
  • Free Testosterone [ Time Frame: Change Measures: Baseline & 6 Months ]
    Free Testosterone measured in ng/dL
  • Dehydroepiandrosterone Sulfate (DHEAS) [ Time Frame: Change Measures: Baseline & 6 Months ]
    DHEAS measured in mcg/dL
  • Body Mass Index (BMI) [ Time Frame: Change Measures: Baseline & 6 Months ]
    Body Mass Index measured in kg/m2
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • Oral Glucose Tolerance Test [ Time Frame: Change Measures: Baseline & 6 Months ]
    Measurement of glucose and insulin at baseline and 2 hours after 75g of glucola.
  • Hormone Labs [ Time Frame: Change Measures: Baseline & 6 Months ]
    Ovarian and Adrenal Androgens
  • Menstrual History [ Time Frame: Change Measures: Baseline & 6 Months ]
    Description of menstrual frequency
  • Body Mass Index [ Time Frame: Change Measures: Baseline & 6 Months ]
    kg/m2
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • Functional MRI [ Time Frame: Change Measures: Baseline & 6 Months ]
    Measures brain activity by detecting changes associated with blood flow
  • Trans abdominal Ovarian Ultrasound [ Time Frame: Change Measures: Baseline & 6 Months ]
    Non invasive, exam that produces images of the ovaries
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents
Official Title  ICMJE Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents
Brief Summary To exam in the effect of a combination of low dose Metformin and Spironolactone on functional brain MRI, menstrual regulation and metabolism in adolescents with PCOS.
Detailed Description

Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in adolescent females and also one of the most complex. Patients experience an exaggerated ovarian/adrenal androgen production in response to physiologic and supra-physiologic elevations in insulin. The hormonal dysregulation is not only associated with acne, hirsutism, and menstrual irregularity, but also with perpetuated insulin resistance, central adiposity, and clinical depression.

In the proposed study, we aim to treat a hormonally and metabolically well-defined group of adolescent girls with PCOS with a combination of two pharmacological agents: metformin (insulin sensitizer) and spironolactone (anti-androgen) for 6 months. Although hyperandrogenism is a fundamental component of PCOS and responsible for the perpetuation of insulin resistance, adiposity and anovulation, there are few pediatric studies that have examined the benefits of treating both insulin resistance and hyperandrogenism simultaneously. Preliminary studies in adults, however, suggest synergistic effect of both spironolactone and metformin (spiro-met) with near normalization of the metabolic and ovulatory dysfunction. Therefore, we hypothesize that spiro-met will improve adolescent metabolism, body composition, ovarian morphology/function. We anticipate that our study will generate key pilot data for further randomized, double blind placebo controlled trials using both agents.

We also plan to examine functional brain MRI before and after the spiro-met intervention. This will allow us to inspect the effects of the hyperinsulinemic/androgenic hormonal milieu in PCOS on structural and functional brain MRI. We hypothesis, that the hormonal environment in PCOS affects centers of appetite and mood.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE PCOS
Intervention  ICMJE Drug: Metformin and Spironolactone
Oral Metformin tablet (500 mg/tablet) twice daily for 6 months. Oral Spironolactone tablet (50 mg/tablet) once daily for 6 months.
Study Arms  ICMJE Experimental: Overall Study
Treatment with Metformin and Spironolactone
Intervention: Drug: Metformin and Spironolactone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 4, 2021) 		12
Original Actual Enrollment  ICMJE
 (submitted: June 7, 2019) 		13
Actual Study Completion Date  ICMJE June 5, 2019
Actual Primary Completion Date July 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Generally healthy
  • Meeting Androgen Excess Society (AES) diagnostic criteria of PCOS: Menstrual Dysfunction or PCO ovaries on ultrasound AND clinical or biochemical hyperandrogenism
  • Normal liver and kidney function
  • No chronic illnesses except for stable, treated hypothyroidism

Exclusion Criteria:

  • Use of metformin and/or spironolactone within the last 6 months
  • Currently on either oral hormonal contraception or other forms of hormonal contraception such as Depo-Provera, NuvaRing
  • Current or past pregnancy
  • Currently sexually active
  • Psychiatric disorder based on self/parental report
  • Type 2 diabetes (blood glucose > 200mg/dl on OGTT)
  • Anemia (Hct < 35)
  • Impaired kidney function (Baseline creatinine > 1.0 mg)
  • Abnormal liver transaminases > 2 x the upper limit of normal range
  • Potassium elevated outside the reference range (in non-hemolyzed blood sample)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 13 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03981861
Other Study ID Numbers  ICMJE 16010020
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Children's Mercy Hospital Kansas City
Study Sponsor  ICMJE Children's Mercy Hospital Kansas City
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tania Burgert, MD Children's Mercy Hospital Kansas City
PRS Account Children's Mercy Hospital Kansas City
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯